van der Heijden Joyce E M, Freriksen Jolien J M, de Hoop-Sommen Marika A, Greupink Rick, de Wildt Saskia N
Division of Pharmacology and Toxicology, Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Pediatric and Neonatal Intensive Care, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands.
Clin Pharmacol Ther. 2023 Nov;114(5):960-971. doi: 10.1002/cpt.3023. Epub 2023 Sep 5.
It is well-accepted that off-label drug dosing recommendations for pediatric patients should be based on the best available evidence. However, the available traditional evidence is often low. To bridge this gap, physiologically-based pharmacokinetic (PBPK) modeling is a scientifically well-founded tool that can be used to enable model-informed dosing (MID) recommendations in children in clinical practice. In this tutorial, we provide a pragmatic, PBPK-based pediatric modeling workflow. For this approach to be successfully implemented in pediatric clinical practice, a thorough understanding of the model assumptions and limitations is required. More importantly, careful evaluation of an MID approach within the context of overall benefits and the potential risks is crucial. The tutorial is aimed to help modelers, researchers, and clinicians, to effectively use PBPK simulations to support pediatric drug dosing.
人们普遍认为，针对儿科患者的非标签药物给药建议应基于现有最佳证据。然而，现有的传统证据往往质量较低。为了弥合这一差距，基于生理的药代动力学（PBPK）建模是一种有科学依据的工具，可用于在临床实践中为儿童提供模型指导给药（MID）建议。在本教程中，我们提供了一个基于PBPK的实用儿科建模工作流程。要使这种方法在儿科临床实践中成功实施，需要全面了解模型假设和局限性。更重要的是，在综合考虑总体益处和潜在风险的背景下，仔细评估MID方法至关重要。本教程旨在帮助建模人员、研究人员和临床医生有效使用PBPK模拟来支持儿科药物给药。
